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2020 ; 8
(7
): 687-695
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gab.com Text
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English Wikipedia
Tropism, replication competence, and innate immune responses of the coronavirus
SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and
in-vitro cultures
#MMPMID32386571
Hui KPY
; Cheung MC
; Perera RAPM
; Ng KC
; Bui CHT
; Ho JCW
; Ng MMT
; Kuok DIT
; Shih KC
; Tsao SW
; Poon LLM
; Peiris M
; Nicholls JM
; Chan MCW
Lancet Respir Med
2020[Jul]; 8
(7
): 687-695
PMID32386571
show ga
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged
in December 2019, causing a respiratory disease (coronavirus disease 2019,
COVID-19) of varying severity in Wuhan, China, and subsequently leading to a
pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly
understood. We evaluate its tissue and cellular tropism in human respiratory
tract, conjunctiva, and innate immune responses in comparison with other
coronavirus and influenza virus to provide insights into COVID-19 pathogenesis.
METHODS: We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and
compared virus tropism and replication competence with SARS-CoV, Middle East
respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic
influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung
(n=4). We assessed extrapulmonary infection using ex-vivo cultures of human
conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell
lines. Innate immune responses and angiotensin-converting enzyme 2 expression
were investigated in human alveolar epithelial cells and macrophages. In-vitro
studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and
mock-infected cells as controls. FINDINGS: SARS-CoV-2 infected ciliated,
mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in
the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication
competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than
H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm,
but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater
than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines
than H5N1, H1N1pdm, or MERS-CoV. INTERPRETATION: The conjunctival epithelium and
conducting airways appear to be potential portals of infection for SARS-CoV-2.
Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium;
SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These
findings provide important insights into the transmissibility and pathogenesis of
SARS-CoV-2 infection and differences with other respiratory pathogens. FUNDING:
US National Institute of Allergy and Infectious Diseases, University Grants
Committee of Hong Kong Special Administrative Region, China; Health and Medical
Research Fund, Food and Health Bureau, Government of Hong Kong Special
Administrative Region, China.